In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

As the population is aging rapidly,the incidence of Alzheimer's disease(AD)is increasing year by year.The World Health Organization stresses that early prevention plays a key role in reducing the incidence of AD.Subjective cognitive decline(SCD)is an early window of AD development,and timely intervention can effectively slow down the progression of the disease or prevent it from developing into dementia,thus reducing the burden on the society.White matter hyperintensity(WMH)can effectively reflect white matter changes and provide strong evidence to identify SCD.In this paper,we review the recent research progress in WMH and SCD,reveal the problems in the current research on WMH,explain the correlation between WMH and SCD in terms of physiopathology and cognitive function,and put forward several suggestions for the future research.
Humans ; White Matter/pathology* ; Cognitive Dysfunction/pathology* ; Alzheimer Disease/pathology* ; Magnetic Resonance Imaging

Objective:To explore the mediating effect of psychological resilience between perceived stress and job burnout among standardized gastroenterology nursing training students.Methods:A total of 156 nursing trainees who received standardized training in the Department of Gastroenterology at Shaanxi Provincial People's Hospital between December 2022 and July 2024 were selected by the convenience sampling method. Data were collected using a general information questionnaire, the Connor-Davidson Resilience Scale, the Chinese Perceived Stress Scale, and the Maslach Burnout Inventory-General Survey. A Pearson correlation analysis was used to examine the relationship among perceived stress, psychological resilience, and job burnout in standardized gastroenterology nursing training students. AMOS 24.0 statistical software was used to construct a structural equation model to analyze the mediating effect of psychological resilience between perceived stress and job burnout in standardized gastroenterology nursing training students. The bias-corrected bootstrap method was applied to test the mediating effect of psychological resilience.Results:The averaged total scores of 156 standardized gastroenterology nursing training students were (29.89±0.30) for perceived pressure, (62.45±2.44) for psychological resilience, and (57.85±3.44) for job burnout. Of the trainees, 88 (56.41%) exhibited job burnout, including 39 (25.00%) with mild burnout, 41 (26.28%) with moderate burnout, and 8 (5.13%) with severe burnout. The Pearson correlation analysis showed that perceived stress was positively correlated with job burnout ( r=0.543, P<0.05) and negatively correlated with psychological resilience ( r=-0.443, P<0.05), and psychological resilience was negatively correlated with job burnout ( r=-0.478, P<0.05). The results of bias-corrected bootstrap test showed that psychological resilience had a partial mediating effect between perceived stress and job burnout among standardized gastroenterology nursing training students ( P<0.05), accounting for 32.63% of the total effect. Conclusions:Moderate job burnout was observed in standardized gastroenterology nursing training students. Job burnout was closely related to perceived stress and psychological resilience. Psychological resilience partly mediated the relationship between perceived stress and job burnout. Therefore, clinical managers may alleviate the perceived psychological pressure and subsequently reduce the occurrence of job burnout among standardized nursing training students by increasing psychological resilience.

Objective·To investigate the efficacy and safety of a dose-reduced,all-oral lenalidomide/melphalan/prednisone acetate(RMP)regimen in elderly and frail patients with newly diagnosed multiple myeloma(NDMM).Methods·Elderly and frail NDMM patients who visited the Department of Hematology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and the Third People's Hospital of Kunshan from April 2018 to March 2024 were retrospectively included.Clinical data and laboratory indicators were collected,and all patients were treated with the RMP regimen.SPSS 27.0 and R software were used for statistical analysis.Independent t-test was applied to normally distributed quantitative data,Mann-Whitney U test to non-normally distributed quantitative data,and x2 test and Fisher's exact probability method to qualitative data.Kaplan-Meier survival curves and Log-rank test were used for survival analysis.Results·Among the 22 elderly and frail NDMM patients treated with RMP,the median age was 76.3(68.4,95.0)years,and the median follow-up time was 25.5 months.The overall response rate(ORR)was 68.2%,and the rate of≥very good partial response(VGPR)was 36.4%.The median progression-free survival(PFS)was 20.53 months.The median PFS in the≤75-year-old group was 25.23(95%CI 12.95?37.52)months,while in the>75-year-old group it was 18.23(95%CI 14.86?21.61)months.There was no significant difference between the two groups.The median PFS in the≥partial response(PR)group was 20.67(95%CI 13.57?27.76)months,and in the

Objective To examine overall adaptive behavior,structural profiles and teacher-parent rating differences in children with intellectual disability(ID)and autism spectrum disorder(ASD),and to explore the association between adaptive behavior and intellectual level.Methods From March to June,2024,65 children with intellectual and developmental disabilities from Handan Special Education Center School,Xingtai Special Education School and Zhengding County Special Education School were selected and 57 valid cases were retained,who were divided into ID group(n=37)and ASD group(n=20).Adaptive behavior was assessed using the Chinese version of Adaptive Behavior Assessment System-II(ABAS-II)by parents and teachers familiar with the children.Group differences were compared,teacher-parent rating consistency was evaluated,and the relationship between adaptive behavior and intelligence quotient(IQ)was examined.Results Mean General Adaptive Composite(GAC)scores were significantly below normative values,as well as all three domains and specific skill subsets underperforming.ASD group exhibited higher self-management scores but lower community application scores than in ID group.Teacher-parent ratings showed moderate-to-high correla-tion across dimensions,which was mainly stronger in ASD group than ID group.IQ demonstrated significant pos-itive correlations with GAC and all three domain scores(rs=0.82 to 0.91,P<0.001).Conclusion Children with intellectual and developmental disabilities show markedly lower levels of adaptive behavior than their typically developing peers.Parents generally rate adaptive behaviors higher than teachers.Both ID and ASD groups exhibited a developmental pattern that practical skills are strongest,followed by social skills,while conceptual skills are weakest.Specific skills such as self-care,health/safety and school/home living were relative-ly stronger,while learning function,social interaction and community application lagging.ASD children under-perform in community application compared to ID peers but outperform in self-management.Adaptive behavior is closely tied to intellectual functioning.ABAS-II results may serve as a reference for assessing disability severi-ty in practice.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia. METHODS: Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry. RESULTS: DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABA_A receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01). CONCLUSION DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABA_A receptors expressions and GA/GABA ratio.
Animals ; Dendrobium/chemistry* ; Rats, Sprague-Dawley ; Male ; Sleep Initiation and Maintenance Disorders/blood* ; Plant Extracts/therapeutic use* ; Receptors, GABA-A/metabolism* ; Noise/adverse effects* ; Light/adverse effects* ; gamma-Aminobutyric Acid/metabolism* ; Sleep/drug effects* ; Rats ; Receptors, GABA/metabolism*

Objective·To investigate the efficacy and safety of a dose-reduced,all-oral lenalidomide/melphalan/prednisone acetate(RMP)regimen in elderly and frail patients with newly diagnosed multiple myeloma(NDMM).Methods·Elderly and frail NDMM patients who visited the Department of Hematology of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and the Third People's Hospital of Kunshan from April 2018 to March 2024 were retrospectively included.Clinical data and laboratory indicators were collected,and all patients were treated with the RMP regimen.SPSS 27.0 and R software were used for statistical analysis.Independent t-test was applied to normally distributed quantitative data,Mann-Whitney U test to non-normally distributed quantitative data,and x2 test and Fisher's exact probability method to qualitative data.Kaplan-Meier survival curves and Log-rank test were used for survival analysis.Results·Among the 22 elderly and frail NDMM patients treated with RMP,the median age was 76.3(68.4,95.0)years,and the median follow-up time was 25.5 months.The overall response rate(ORR)was 68.2%,and the rate of≥very good partial response(VGPR)was 36.4%.The median progression-free survival(PFS)was 20.53 months.The median PFS in the≤75-year-old group was 25.23(95%CI 12.95?37.52)months,while in the>75-year-old group it was 18.23(95%CI 14.86?21.61)months.There was no significant difference between the two groups.The median PFS in the≥partial response(PR)group was 20.67(95%CI 13.57?27.76)months,and in the